RESUMO
Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of renal impairment resulting from mutations in the MUC1, UMOD, HNF1B, REN, and SEC61A1 genes. Neither the national or global prevalence of these diseases has been determined. We aimed to establish a database of patients with ADTKD in Ireland and report the clinical and genetic characteristics of these families. Methods: We identified patients via the Irish Kidney Gene Project and referral to the national renal genetics clinic in Beaumont Hospital who met the clinical criteria for ADTKD (chronic kidney disease, bland urinary sediment, and autosomal dominant inheritance). Eligible patients were then invited to undergo genetic testing by a variety of methods including panel-based testing, whole exome sequencing and, in five families who met the criteria for diagnosis of ADTKD but were negative for causal genetic mutations, we analyzed urinary cell smears for the presence of MUC1fs protein. Results: We studied 54 individuals from 16 families. We identified mutations in the MUC1 gene in three families, UMOD in five families, HNF1beta in two families, and the presence of abnormal MUC1 protein in urine smears in three families (one of which was previously known to carry the genetic mutation). We were unable to identify a mutation in 4 families (3 of whom also tested negative for urinary MUC1fs). Conclusions: There are 4443 people with ESRD in Ireland, 24 of whom are members of the cohort described herein. We observe that ADTKD represents at least 0.54% of Irish ESRD patients.
Assuntos
Genes Dominantes , Falência Renal Crônica/genética , Túbulos Renais/patologia , Adulto , Idoso , Estudos Transversais , Feminino , Testes Genéticos/estatística & dados numéricos , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , Irlanda/epidemiologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Mucina-1/genética , Mutação , Prevalência , Uromodulina/genéticaRESUMO
Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with nephropathy in African Americans (AAs). The effect of transplanting kidneys from AA donors with two APOL1 nephropathy risk variants is unknown. APOL1 risk variants were genotyped in 106 AA deceased organ donors and graft survival assessed in 136 resultant kidney transplants. Cox-proportional hazard models tested for association between time to graft failure and donor APOL1 genotypes. The mean follow-up was 26.4 ± 21.8 months. Twenty-two of 136 transplanted kidneys (16%) were from donors with two APOL1 nephropathy risk variants. Twenty-five grafts failed; eight (32%) had two APOL1 risk variants. A multivariate model accounting for donor APOL1 genotype, overall African ancestry, expanded criteria donation, recipient age and gender, HLA mismatch, CIT and PRA revealed that graft survival was significantly shorter in donor kidneys with two APOL1 risk variants (hazard ratio [HR] 3.84; p = 0.008) and higher HLA mismatch (HR 1.52; p = 0.03), but not for overall African ancestry excluding APOL1. Kidneys from AA deceased donors harboring two APOL1 risk variants failed more rapidly after renal transplantation than those with zero or one risk variants. If replicated, APOL1 genotyping could improve the donor selection process and maximize long-term renal allograft survival.
Assuntos
Apolipoproteínas/genética , Transplante de Rim/métodos , Lipoproteínas HDL/genética , Insuficiência Renal/etnologia , Insuficiência Renal/terapia , Adulto , Negro ou Afro-Americano , Apolipoproteína L1 , Feminino , Seguimentos , Genótipo , Glomerulosclerose Segmentar e Focal/imunologia , Sobrevivência de Enxerto , Antígenos HLA/imunologia , Humanos , Imunossupressores/uso terapêutico , Rim/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Risco , Doadores de Tecidos , Transplante HomólogoRESUMO
AIMS: To determine the effect of sickle cell trait on measurement of glycated haemoglobin (HbA(1c)) in African American patients with diabetes mellitus. METHODS: This is a retrospective study including 885 outpatients who underwent HbA(1c) testing. Medical record review and sickle cell trait determinations based on the HbA(1c) assay were performed in African American participants. The relationship between HbA(1c) and serum glucose measurements was analysed. RESULTS: Data were obtained from 385 AA (109 with SCT, 22 with haemoglobin C trait and 254 without haemoglobinopathy) and 500 European American patients. In a model created through multivariate repeated-effects regression, the relationship between HbA(1c) and simultaneous serum glucose did not differ between African American subjects with and without the sickle cell trait, but differed between African American subjects without the sickle cell trait and European Americans (P = 0.0002). CONCLUSIONS: Sickle cell trait does not impact the relationship between HbA(1c) and serum glucose concentration. In addition, it does not appear to account for ethnic difference in this relationship between African Americans and whites.
Assuntos
Negro ou Afro-Americano , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/análise , Traço Falciforme/sangue , População Branca , Diabetes Mellitus Tipo 2/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Traço Falciforme/etnologiaRESUMO
INTRODUCTION: Although African Americans (AA) are considered higher risk kidney donors than Caucasians, limited data are available regarding outcomes of AA donors. METHODS: We performed a single-center retrospective review of all kidney donors from 1993 to 2007 and evaluated race/ethnic differences in post-donation changes in renal function, incident proteinuria, and systolic blood pressure (SBP) using linear mixed models. RESULTS: A total of 336 kidney donors (63 AA, 263 Caucasian, 10 other) were evaluated. Before donation, AA had higher serum creatinine concentrations, estimated glomerular filtration rate (GFR) values, and SBP levels than Caucasians. No significant changes in SBP or renal function were observed between the two groups within the first year after donation, although results were limited by incomplete follow-up. CONCLUSION: AA had higher pre-donation serum creatinine, GFR, and SBP values compared to Caucasians; however, the degree of change in renal function and blood pressure did not differ between groups following kidney donation. Although long-term studies are needed, our study suggests that AA and Caucasians experience similar short-term consequences after donation. The incomplete data available on donor outcomes in our center and in prior publications also indicates a global need to implement systems for structured follow-up of live kidney donors.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Sobrevivência de Enxerto , Transplante de Rim , Rim/fisiologia , Doadores Vivos , População Branca/estatística & dados numéricos , Adulto , Pressão Sanguínea , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Prognóstico , Proteinúria/diagnóstico , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: A family was identified with autosomal dominant inheritance of anemia, polyuria, hyperuricemia, and chronic kidney disease. Mutational analysis revealed a novel heterozygous mutation c.58T > C resulting in the amino acid substitution of cysteine for arginine in the preprorenin signal sequence (p.cys20Arg) occurring in all affected members. METHODS: Effects of the identified mutation were characterized using in vitro and in vivo studies. Affected individuals were clinically characterized before and after administration of fludrocortisone. RESULTS: The mutation affects endoplasmic reticulum co-translational translocation and posttranslational processing, resulting in massive accumulation of non-glycosylated preprorenin in the cytoplasm. This affects expression of intra-renal RAS components and leads to ultrastructural damage of the kidney. Affected individuals suffered from anemia, hyperuricemia, decreased urinary concentrating ability, and progressive chronic kidney disease. Treatment with fludrocortisone in an affected 10-year-old child resulted in an increase in blood pressure and estimated glomerular filtration rate. CONCLUSIONS: A novel REN gene mutation resulted in an alteration in the amino acid sequence of the renin signal sequence and caused childhood anemia, polyuria, and kidney disease. Treatment with fludrocortisone improved renal function in an affected child. Nephrologists should consider REN mutational analysis in families with autosomal dominant inheritance of chronic kidney disease, especially if they suffer from anemia, hyperuricemia, and polyuria in childhood.
Assuntos
Fludrocortisona/uso terapêutico , Genes Dominantes , Nefropatias/tratamento farmacológico , Nefropatias/genética , Mutação , Sinais Direcionadores de Proteínas/genética , Renina/genética , Adulto , Sequência de Aminoácidos , Anemia/genética , Anemia/metabolismo , Sequência de Bases , Biópsia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética , Linhagem Celular , Criança , Doença Crônica , Quimosina , Citoplasma/metabolismo , Análise Mutacional de DNA , Retículo Endoplasmático/metabolismo , Precursores Enzimáticos , Feminino , Predisposição Genética para Doença , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/genética , Glicosilação , Heterozigoto , Humanos , Hiperuricemia/genética , Hiperuricemia/metabolismo , Hipoaldosteronismo/genética , Hipoaldosteronismo/metabolismo , Capacidade de Concentração Renal/genética , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/fisiopatologia , Masculino , Dados de Sequência Molecular , Linhagem , Fenótipo , Poliúria/genética , Poliúria/metabolismo , Processamento de Proteína Pós-Traducional , Transporte Proteico , Renina/metabolismo , Transfecção , Resultado do TratamentoRESUMO
AIMS: To determine if the relationship between serum glucose concentration and glycated haemoglobin is different between African-Americans and whites. METHODS: Retrospective cross-sectional study comparing the association between glycated haemoglobin and serum glucose levels, based upon ethnicity. Two databases were evaluated: (i) 4215 African-American and 6359 white outpatients who had simultaneous glycated haemoglobin, random serum glucose and creatinine concentration measurements between 2000 and 2007 at the North Carolina Baptist Hospital and (ii) 1021 white and 312 African-American Diabetes Heart Study (DHS) participants. RESULTS: In North Carolina Baptist Hospital clinic attendees, a given glycated haemoglobin was associated with higher serum glucose concentrations in African-Americans compared with whites. In a multivariate model with glycated haemoglobin as the outcome variable, racial differences remained significant after adjustment for serum glucose, age, gender and kidney function. For individuals with a serum glucose between 5.6 and 8.3 mmol/l, the glucose : glycated haemoglobin ratio was 1.03 +/- 0.16 mmol/l/% in white individuals and 0.99 +/- 0.17 mmol/l/% in African-Americans (P < 0.0001). For a glycated haemoglobin value of 7.0%, there was a 0.98-mmol/l difference in predicted serum glucose concentration in 50-year-old African-American men, relative to white. Results were replicated in the DHS, where in a best-fit linear model, after adjustment for glucose, African-American race was a significant predictor of glycated haemoglobin (P < 0.0001). CONCLUSIONS: African-Americans have higher glycated haemoglobin values at given serum glucose concentrations relative to whites. This finding may contribute to the observed difference in glycated haemoglobin values reported between these race groups.
Assuntos
Glicemia/análise , Hemoglobinas Glicadas/análise , População Branca , Adulto , Negro ou Afro-Americano , Idoso , Creatinina/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , North Carolina , Estudos RetrospectivosRESUMO
Glycated albumin is thought to more accurately reflect glycemic control in diabetic hemodialysis patients than hemoglobin A(1c) because of shortened red cell survival. To test this, glycated hemoglobin and albumin levels were measured in blood samples collected from 307 diabetic subjects of whom 258 were on hemodialysis and 49 were without overt renal disease. In diabetic subjects with renal disease, relative to those without, the mean serum glucose and glycated albumin concentrations were significantly higher while hemoglobin A(1c) tended to be lower. The glycated albumin to hemoglobin A(1c) ratio was significantly increased in dialysis patients compared with the controls. Hemoglobin A(1c) was positively associated with hemoglobin and negatively associated with the erythropoietin dose in hemodialysis patients, whereas these factors and serum albumin did not significantly impact glycated albumin levels. Using best-fit multivariate models, dialysis status significantly impacted hemoglobin A(1c) levels without a significant effect on glycated albumin. Our results show that in diabetic hemodialysis patients, hemoglobin A(1c) levels significantly underestimate glycemic control while those of glycated albumin more accurately reflect this control.
Assuntos
Diabetes Mellitus/sangue , Hemoglobinas Glicadas/análise , Diálise Renal , Albumina Sérica/análise , Feminino , Produtos Finais de Glicação Avançada , Humanos , Masculino , Pessoa de Meia-Idade , Albumina Sérica GlicadaRESUMO
Autosomal dominant tubulointerstitial kidney disease (ADTKD) is characterized by autosomal dominant inheritance, progressive chronic kidney disease, and a bland urinary sediment. ADTKD is most commonly caused by mutations in the UMOD gene encoding uromodulin (ADTKD-UMOD). We herein report the first confirmed case of a multi-generational Brazilian family with ADTKD-UMOD, caused by a novel heterozygous mutation (c.163G>A, GGCâAGC, p.Gly55Ser) in the UMOD gene. Of 41 family members, 22 underwent genetic analysis, with 11 individuals found to have this mutation. Three affected individuals underwent hemodialysis, one peritoneal dialysis, and one patient received a kidney transplant from a family member later found to be genetically affected. Several younger individuals affected with the mutation were also identified. Clinical characteristics included a bland urinary sediment in all tested individuals and a kidney biopsy in one individual showing tubulointerstitial fibrosis. Unlike most other reported families with ADTKD-UMOD, neither gout nor hyperuricemia was found in affected individuals. In summary, we report a novel UMOD mutation in a Brazilian family with 11 affected members, and we discuss the importance of performing genetic testing in families with inherited kidney disease of unknown cause.
Assuntos
Mutação/genética , Rim Policístico Autossômico Dominante/genética , Uromodulina/genética , Biópsia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Linhagem , Rim Policístico Autossômico Dominante/patologiaRESUMO
AIMS: Sevelamer carbonate is an anion exchange resin with the same polymeric structure as sevelamer hydrochloride in which carbonate replaces chloride as the anion. The study investigated the effects of sevelamer carbonate and sevelamer hydrochloride on serum phosphorus, lipids and bicarbonate levels in hemodialysis patients. MATERIALS AND METHODS: This was a double-blind, randomized, crossover study. 79 hemodialysis patients were randomly assigned to either sevelamer carbonate or sevelamer hydrochloride for 8 weeks followed by a crossover to the other regimen for an additional 8 weeks of treatment. RESULTS: The mean serum phosphorus was 4.6+/-0.9 and 4.7+/-0.9 mg/dl during sevelamer carbonate and sevelamer hydrochloride treatment, respectively. Sevelamer carbonate and sevelamer hydrochloride were equivalent in controlling serum phosphorus, the geometric least square mean ratio was 0.99 (90% CI, 0.95-1.03). Mean total and LDL cholesterol were 144.0+/-33.9 and 59.5+/-24.9 mg/dl, respectively, during sevelamer carbonate treatment and 139.0+/-33.6 and 56.0+/-23.3 mg/dl, respectively, during sevelamer hydrochloride treatment. Serum bicarbonate levels increased by 1.3+/-4.1 mEq/l during sevelamer carbonate treatment. There were fewer gastrointestinal adverse events with sevelamer carbonate. CONCLUSIONS: Sevelamer carbonate and sevelamer hydrochloride were equivalent in controlling serum phosphorus and serum bicarbonate levels increased with sevelamer carbonate. Lipid profiles for both were well-below the levels suggested by KDOQI. Sevelamer carbonate may have advantages over sevelamer hydrochloride in the treatment of hyperphosphatemia in hemodialysis patients.
Assuntos
Bicarbonatos/sangue , Quelantes/uso terapêutico , Nefropatias/sangue , Lipídeos/sangue , Fósforo/sangue , Poliaminas/uso terapêutico , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , SevelamerRESUMO
A multicenter phase I-II trial of intravenous (IV) human recombinant interferon beta (rIFN-beta; Betaseron; Triton Bioscience Inc, Almeda, CA) was conducted in children with recurrent or progressive primary brain and spinal cord tumors. A total of 29 patients were enrolled: high-grade astrocytoma (12), brainstem glioma (nine), and primitive neuroectadermal tumor (three), ependymoma (two), germ cell (two), and spinal cord astrocytoma (one). Betaseron was given by IV infusion over 30 minutes 3 times per week (Monday-Wednesday-Friday [MWF]). Four dose levels were studied, and at least three patients were entered at each dose level. The treatment plan began with a three-step dose escalation for each patient over 6 weeks (initiation phase). The dose-escalation schema for the four dose levels was: 50-100-200, 100-200-400, 200-300-500, and 300-400-600 x 10(6) (M) IU/m2. Patients experiencing an objective response or stable disease after 6 weeks entered the maintenance phase at the final escalated dose, ie, 200, 400, 500, or 600 mlU/m2 (MWF). Common transient effects included chills, fever, and fatigue. Dose-limiting toxicities were hematologic, hepatic, and CNS. The maintenance maximum-tolerable dose (MTD) was 500 mlU/m2, ie, dose level 3. Response was assessed at completion of the initiation phase and at 2-month intervals during the maintenance phase. Objective partial responses were seen in patients with high-grade astrocytoma (two) and brain-stem glioma (two). Thus, four of 21 (19%) assessable patients had partial responses for a median of 4 months. Eight patients had stable disease for a median of 5+ (2 to 14+) months. Antineoplastic activity has been identified in children with high-grade astrocytomas and brainstem gliomas in a dose-intensive regimen.
Assuntos
Neoplasias Encefálicas/terapia , Interferon Tipo I/uso terapêutico , Interferon beta , Recidiva Local de Neoplasia/terapia , Proteínas Recombinantes/uso terapêutico , Criança , Avaliação de Medicamentos , Humanos , Interferon Tipo I/efeitos adversos , Interferon beta-1a , Interferon beta-1b , Proteínas Recombinantes/efeitos adversosRESUMO
CSF and plasma antifolate concentrations during 257 intravenous (IV) infusions of high-dose methotrexate were measured in 60 children with acute lymphoblastic leukemia. In 49 children who have never had evidence for CNS leukemia, the mean steady-state CSF to plasma methotrexate ratio was 0.013 (SD = 0.01). In contrast, 11 children with overt meningeal leukemia had a 12-fold higher mean ratio of 0.157 (range, 0.013 to 0.844, p less than .01). In the group of patients studied, all of those with a CSF methotrexate concentration greater than 2 SD above the mean either had leukemic cells in the CSF or subsequently developed this condition. In two patients, overt CNS leukemia was preceded by a high CSF:plasma drug ratio at a time when there was no cytologic or clinical evidence for CNS leukemia. As previously observed with intrathecal methotrexate, we conclude that overt meningeal leukemia increases CSF drug concentrations during IV methotrexate therapy. An elevated CSF to plasma ratio may be useful to predict imminent CNS relapse or to verify completeness of response to therapy.
Assuntos
Leucemia Linfoide/líquido cefalorraquidiano , Neoplasias Meníngeas/líquido cefalorraquidiano , Metotrexato/líquido cefalorraquidiano , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Infusões Parenterais , Leucemia Linfoide/sangue , Leucemia Linfoide/tratamento farmacológico , Masculino , Neoplasias Meníngeas/diagnóstico , Metotrexato/administração & dosagem , Metotrexato/sangue , Prognóstico , Análise de RegressãoRESUMO
An intensive multimodal therapy was developed for the treatment of a subpopulation of children with acute lymphoblastic leukemia (ALL) who had a predicted event-free survival of less than 40% on previously reported therapeutic regimens (at high risk for early relapse). Induction with multiagent chemotherapy and radiotherapy to bulky disease-bearing areas (peripheral lymph nodes and mediastinum) was followed by consolidation, CNS prophylaxis, and cyclical remission maintenance therapy. Ninety-six (96%) of 100 previously untreated patients, 1 to 17 years of age, attained a complete remission. Seven patients received other maintenance therapy or a bone marrow transplant in remission. Sixty-six of the remaining 89 (74%) are in continuous complete remission at 22+ to 72+ months (median, 44+ months). Marrow relapse occurred in 15 (17%), CNS relapse in 5 (6%), and testicular relapse in one. Sixty-six of the 93 evaluable patients (71%) (including the induction failures) are event-free survivors. Two patients died of infection during the induction phase. No patient died during consolidation or maintenance without recurrent disease. The patients spent a median of 19, 0, and 0 days hospitalized during induction, consolidation, and maintenance, respectively. The most common complications were bacteremia and mucositis during induction and mucositis and fever during periods of neutropenia in consolidation. Maintenance was well tolerated. We conclude that the treatment protocol is intensive, but the inherent toxicities are manageable with adequate supportive care. The life table--projected event-free survival of 69% +/- 5% 48 months from diagnosis is encouraging.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfoide/mortalidade , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Asparaginase/administração & dosagem , Transplante de Medula Óssea , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Feminino , Humanos , Lactente , Leucemia Linfoide/terapia , Masculino , Metotrexato/administração & dosagem , Prednisona/administração & dosagem , Prognóstico , Dosagem Radioterapêutica , Recidiva , Risco , Tioguanina/administração & dosagem , Fatores de Tempo , Vincristina/administração & dosagemRESUMO
INTRODUCTION: Medullary cystic kidney disease 2 (MCKD2) and familial juvenile hyperuricaemic nephropathy (FJHN) are both autosomal dominant renal diseases characterised by juvenile onset of hyperuricaemia, gout, and progressive renal failure. Clinical features of both conditions vary in presence and severity. Often definitive diagnosis is possible only after significant pathology has occurred. Genetic linkage studies have localised genes for both conditions to overlapping regions of chromosome 16p11-p13. These clinical and genetic findings suggest that these conditions may be allelic. AIM: To identify the gene and associated mutation(s) responsible for FJHN and MCKD2. METHODS: Two large, multigenerational families segregating FJHN were studied by genetic linkage and haplotype analyses to sublocalise the chromosome 16p FJHN gene locus. To permit refinement of the candidate interval and localisation of candidate genes, an integrated physical and genetic map of the candidate region was developed. DNA sequencing of candidate genes was performed to detect mutations in subjects affected with FJHN (three unrelated families) and MCKD2 (one family). RESULTS: We identified four novel uromodulin (UMOD) gene mutations that segregate with the disease phenotype in three families with FJHN and in one family with MCKD2. CONCLUSION: These data provide the first direct evidence that MCKD2 and FJHN arise from mutation of the UMOD gene and are allelic disorders. UMOD is a GPI anchored glycoprotein and the most abundant protein in normal urine. We postulate that mutation of UMOD disrupts the tertiary structure of UMOD and is responsible for the clinical changes of interstitial renal disease, polyuria, and hyperuricaemia found in MCKD2 and FJHN.
Assuntos
Hiperuricemia/genética , Mucoproteínas/genética , Mutação/genética , Rim Policístico Autossômico Dominante/genética , Insuficiência Renal/genética , Alelos , Sequência de Bases , Pré-Escolar , Mapeamento Cromossômico , Cromossomos Humanos Par 16/genética , Análise Mutacional de DNA , Éxons/genética , Feminino , Marcadores Genéticos/genética , Gota/genética , Gota/fisiopatologia , Haplótipos/genética , Humanos , Hiperuricemia/fisiopatologia , Escore Lod , Masculino , Linhagem , Fenótipo , Mapeamento Físico do Cromossomo , Rim Policístico Autossômico Dominante/fisiopatologia , Insuficiência Renal/fisiopatologia , UromodulinaRESUMO
In patients who have a linear decline in renal function over time, plotting the reciprocal serum creatinine versus time has been found to be useful in monitoring renal disease progression and predicting the start of dialysis. Unfortunately, producing such plots is cumbersome because of the inherent difficulties of plotting a reciprocal number on standard graph paper. This technical note presents a graph in which the y-axis is represented as a reciprocal axis. In this manner, one is able to directly plot the serum creatinine over time and must not rely on plotting the reciprocal value. This approach may make the plotting of such data easier for the nephrologist and make this clinical tool more useful.
Assuntos
Creatinina/sangue , Documentação/métodos , Falência Renal Crônica/diagnóstico , Testes de Função Renal , Registros Médicos Orientados a Problemas , Seguimentos , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Diálise RenalRESUMO
The purpose of this study is to better characterize graft and patient survival posttransplantation by examining survival according to underlying renal disease for all first-time renal allograft recipients in the United Network for Organ Sharing (UNOS) registry. From 1987 through 1996, the UNOS registry collected data on 23,838 living and 67,183 cadaveric renal transplantations. This investigation included all patients undergoing their first renal transplantation for whom the underlying cause of renal failure could be identified and categorized. Gross 1- and 3-year patient and graft survival according to underlying renal disease are included. In addition, a Cox proportional hazards model was created to analyze the effect of underlying disease on graft and patient survival after adjusting for comorbid conditions, demographics, and type of renal transplant (living versus cadaveric). The association between underlying disease and graft and patient survival is shown. Amyloidosis, sickle cell anemia, scleroderma, and radiation nephritis are associated with poor graft and patient survival. The risk ratio for patient mortality was more than twice that for immunoglobulin A nephropathy for a number of conditions, including analgesic nephropathy, amyloidosis, and both forms of diabetes mellitus.
Assuntos
Nefropatias/patologia , Transplante de Rim , Sobrevivência de Enxerto , Humanos , Modelos de Riscos Proporcionais , Sistema de Registros/estatística & dados numéricos , Análise de Sobrevida , Fatores de TempoRESUMO
The purpose of this investigation was to describe the clinical presentation of nine patients with calciphylaxis involving the proximal lower extremities or trunk and to compare the clinical characteristics of these patients with those of 347 hemodialysis patients from the same geographic area. Patients were identified primarily through a computer search of pathology records, identifying patients with the term "calciphylaxis" in the biopsy report. All patients had pathologic specimens consistent with calciphylaxis. All the calciphylaxis patients were white and were markedly obese. While two patients had markedly elevated parathyroid hormone levels, most patients did not show severe derangements of calcium phosphate metabolism compared with other dialysis patients. A logistic regression model identified body mass index and low serum albumin 3 months before diagnosis as being highly associated with a diagnosis of calciphylaxis. Diabetes mellitus and parameters of calcium-phosphate metabolism were not significantly associated with proximal calciphylaxis. These findings suggest that white race, morbid obesity, and poor nutritional status are associated with proximal calciphylaxis in dialysis patients.
Assuntos
Calciofilaxia/etiologia , Diálise Renal , Idoso , Biópsia , Calciofilaxia/patologia , Calciofilaxia/fisiopatologia , Cálcio/sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , Obesidade Mórbida/fisiopatologia , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Fatores de Risco , Pele/patologia , População BrancaRESUMO
Although there has been much discussion regarding the etiology of hypertensive renal disease, clinical characteristics of this condition have not been thoroughly studied. The purpose of this investigation was to identify clinical correlates of hypertensive end-stage renal disease (ESRD) in a population of patients older than 50 years and to compare these clinical findings with those in a group of ESRD patients with certain known disorders (established diagnoses). Data regarding demographics, cause of ESRD, educational level, presence of diabetes mellitus, angina, myocardial infarction, and peripheral vascular disease were obtained from the Southeastern Kidney Council for patients starting renal replacement therapy between January 1, 1990, and August 1, 1996. Clinical characteristics were compared for white and black patients. Demographic variables and comorbid conditions were compared between groups with general linear regression or logistic regression contrast techniques. A logistic regression model was formed with hypertensive ESRD or established diagnoses as the outcome variable and comorbid and socioeconomic variables as the independent variables. Hypertensive ESRD was diagnosed in 24% of white and 38% of black patients, while established diagnoses were present in 17% of white and 7% of black ESRD patients. The most common established diagnoses were polycystic kidney disease, specified glomerulonephritis, and nephrolithiasis or obstruction. In a logistic regression model, white patients were found more likely to be classified as having hypertensive ESRD if they were older, suffered from angina and other forms of atherosclerosis, smoked, and were less educated. White patients with hypertensive ESRD were more than 2.4 times as likely to suffer from angina as patients with established diagnoses. For black patients, the presence of peripheral vascular disease and female gender were associated with an increased chance of being diagnosed as having hypertensive ESRD. The results of this investigation show that there is a strong association between atherosclerosis and hypertensive ESRD in older white patients. In black patients, the association between atherosclerosis and hypertensive ESRD was also present, but not as strong. The unique association of hypertensive ESRD with atherosclerosis suggests that atherosclerosis is a risk factor for chronic renal failure and that a primary renal microvascular disorder may lead to both hypertension and progressive renal insufficiency.
Assuntos
Hipertensão/etnologia , Falência Renal Crônica/etnologia , Fatores Etários , Idoso , Arteriosclerose/epidemiologia , População Negra , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Hipertensão/complicações , Hipertensão/terapia , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Terapia de Substituição Renal , Fatores de RiscoRESUMO
Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia and aluminum-based binders that result in total body aluminum accumulation over time. This investigation describes the use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis patients and compares it with a standard calcium-based phosphate binder. An open-label, randomized, crossover study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients. After a 2-week phosphate binder washout period, stable hemodialysis patients were administered either sevelamer or calcium acetate, and the dosages were titrated upward to achieve improved phosphate control over an 8-week period. After a 2-week washout period, patients crossed over to the alternate agent for 8 weeks. Eighty-four patients from eight centers participated in the study. There was a similar decrease in serum phosphate values over the course of the study with both sevelamer (-2.0 +/- 2.3 mg/dL) and calcium acetate (-2.1 +/- 1.9 mg/dL). Twenty-two percent of patients developed a serum calcium greater than 11.0 mg/dL while receiving calcium acetate, versus 5% of patients receiving sevelamer (P < 0.01). The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period. Patients treated with sevelamer also sustained a 24% mean decrease in serum low-density lipoprotein cholesterol levels. Sevelamer was effective in controlling hyperphosphatemia without resulting in an increase in the incidence of hypercalcemia seen with calcium acetate. This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients, and its usage may be advantageous in the treatment of dialysis patients.
Assuntos
Ácido Acético/uso terapêutico , Fosfatos/sangue , Distúrbios do Metabolismo do Fósforo/tratamento farmacológico , Poliaminas/uso terapêutico , Diálise Renal , Cápsulas , LDL-Colesterol/sangue , Estudos Cross-Over , Avaliação de Medicamentos , Feminino , Géis , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We report a patient with pre-existing end-stage renal disease (ESRD) who underwent successful matched related donor allogeneic bone marrow transplantation for AML in second complete remission (CR2) using conditioning with high-dose cyclophosphamide (CY, 60 mg/kg/day x 2) and TBI (165 cGy twice daily x 4 days). The timing of hemodialysis after high-dose CY was extrapolated from available data on the pharmacokinetics of high-dose CY and hemodialysis clearance of conventional dose CY and its metabolites. Pharmacokinetic analyses indicated that the elimination of high-dose CY and its alkylating metabolites is impaired in ESRD but is cleared with hemodialysis. The patient's early post-transplant course was uncomplicated, and WBC and platelet engraftment occurred by day +22. Bone marrow examination on day +25 showed trilineage engraftment with no AML; cytogenetics showed 100% donor karyotype. The patient remains in remission with 100% donor karyotype at 3 years post transplant. Clinical results indicate that the administration of high-dose CY is feasible with hemodialysis support for patients with ESRD.
Assuntos
Transplante de Medula Óssea , Ciclofosfamida/uso terapêutico , Falência Renal Crônica/terapia , Leucemia Mieloide Aguda/terapia , Diálise Renal , Condicionamento Pré-Transplante , Adulto , Ciclofosfamida/farmacocinética , Humanos , Falência Renal Crônica/metabolismo , Masculino , Transplante HomólogoRESUMO
Many of the potential effects of antihypertensive therapy, including renal function, have been inadequately investigated in clinical trials in older adults. In an observational study, we examined the association between treatment with various classes of antihypertensive agents and 3-year changes in serum creatinine in 1296 older adults with treated hypertension and without prior renal disease (mean age 72.2 years; 60% female; 30% diabetic; 42% with cardiovascular disease (CVD)) from the Cardiovascular Health Study. Baseline antihypertensive medications included thiazides (HCT), beta-adrenergic blockers, angiotensin converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), vasodilators (VAS), HCT + BB, HCT + ACE-I, HCT + CCB, HCT + VAS, loop diuretics (LOOP), and other combinations. Unadjusted results indicated that minimal changes in mean serum creatinine occurred over time for all therapies and only a few changes were statistically significant (HCT: +0.02 mg/dL, ACE-I: +0.04, CCB: +0.04; all P < .05; LOOP: +0.06 mg/dL; P < .001). In multivariate analyses with HCT users as the reference group and adjusting for baseline serum creatinine, age, sex, smoking, diabetes mellitus, CVD, height, weight, common carotid intima-media thickness, and use of allopurinol, phenytoin, cimetidine, and nonsteroidal antiinflammatory drugs, all of the relative changes were small and statistically nonsignificant except for HCT + VAS users (+0.07 mg/dL; P < .05). When users of the same therapy at baseline and follow-up were restricted, only LOOP users had significant albeit small changes in serum creatinine (+0.05 mg/dL; P < .05). Although results from clinical trials are needed to confirm these findings, these observational data suggest no major differences between specific antihypertensive therapies in 3-year serum creatinine changes in older adults without prior renal disease.